Complications of severe falciparum malaria

• Morbidity and mortality of P. falciparum species is greatest among the malaria species because of its increased parasetemia and its ability to cytoadhere

• Mortality rises once vital organ dysfunction occurs or proportion of erythrocytes infected increases to >3%

• P. falciparum is also known for developing drug resistance to chloroquine, quinine and tetracycline

Complications

• Cerebral malaria• Hypoglycemia• Lactic acidosis• Noncardiogenic pulmonary edema• Renal impairment• Hematologic abnormalities• Liver dysfunction

Cerebral malaria• Coma: characteristic & ominous feature of

falciparum malaria; mortality rate of ~0.1%, but if there is vital-organ dysfunction, mortality rises steeply

• Manifests as diffuse symmetric encephalopathy • Eyes may be divergent • Muscle tone increase or decrease• ~15% have retinal hemorrhages• Convulsions: generalized; occur up to 50% of

children with cerebral malaria

Cerebral malaria

• ~15% of children with cerebral malaria have been reported to suffer neurologic deficit when they regain consciousness:– Hemiplegia– Cerebral palsy– Cortical blindness– Deafness– Impaired cognition and learning

Hypoglycemia

• Common complication of severe malaria• Associated with poor prognosis• Particularly problematic in children and pregnant

women• Results from a failure of hepatic gluconeogenesis

& an ↑ in the consumption of glucose both by host & the malaria parasites

• Quinine & quinidine are powerful stimulants of pancreatic insulin secretion

Lactic acidosis• Commonly coexists with hypoglycemia• Caused by combination of:– Anaerobic glycolysis in tissues where sequestered

parasites interfere with microcirculatory flow– Hypovolemia– Lactate production by the parasites– Failure of hepatic and renal lactate clearance

• Coexisting renal impairment compounds acidosis• Acidotic breathing: sign of poor prognosis• Plasma concentrations of bicarbonate or lactate: best

biochemical prognosticators in severe malaria

Noncardiogenic pulmonary edema

• Mortality rate: >80%• Aggravated by overly vigorous administration

of IV fluid• Can also develop in otherwise- uncomplicated

vivax malaria (recovery is usual)

Renal impairment

• Rare among children• May be related to RBC sequestration

interfering with renal microcirculatory flow & metabolism

• Manifests as acute tubular necrosis• Early dialysis or hemofiltration enhances the

likelihood of a patient’s survival, particularly in acute hypercatabolic renal failure

Hematologic Abnormalities

• Anemia – results from accelerated RBC destruction & removal

by the spleen in conjunction with ineffective erythropoiesis

– both infected & uninfected RBCs show reduced deformability

– ↑ splenic clearance of RBCs• Slight coagulation abnormalities & mild

thrombocytopenia

Liver Dysfunction

• Severe jaundice – more common among adults than children– Results from hemolysis, hepatocyte injury, and

cholestasis

• Hepatic dysfunction contributes to hypoglycemia, lactic acidosis, and impaired drug metabolism